Alinia

[Andiamo1]

Romark Laboratories, a privately-owned biotechnology company, today announced results of a randomized phase II clinical trial showing that 79% of interferon-naïve patients with chronic hepatitis C genotype 4 receiving nitazoxanide plus the standard of care had a sustained virologic response (SVR), or undetectable level of virus, 12 weeks following treatment, compared to 43% of patients receiving the standard of care without nitazoxanide. The patients treated with nitazoxanide also experienced no relapse and no more side effects than patients who received the standard of care. Interim results from this Phase II clinical trial will be presented on Tuesday November 6 in an oral presentation at the 58th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston.

"Patients treated with nitazoxanide responded earlier and maintained their responses without relapse after receiving only 36 weeks of treatment with peginterferon and ribavirin," said Dr. Emmet B. Keeffe, Chief of Hepatology at Stanford University School of Medicine. "These data suggest the emergence of a new therapeutic approach for treating hepatitis C. While more study is needed to confirm these results in a broader population of patients, nitazoxanide appears to increase the potency of interferon without increasing toxicity or inducing resistance."

Study Details
This Phase II randomized, controlled trial was conducted at two centers in Egypt and is part of the company's STEALTH C (Studies to Evaluate Alinia for Treatment of Hepatitis C) clinical development program, which is designed to evaluate the safety and efficacy of nitazoxanide tablets in combination with peginterferon or peginterferon and ribavirin (standard of care) in patients with chronic hepatitis C.

In the trial, 96 treatment-naive patients with chronic hepatitis C genotype 4 were randomized into three groups to receive either 48 weeks of standard of care treatment (n=40), 12 weeks of nitazoxanide followed by 36 weeks of nitazoxanide plus peginterferon (a dual regimen, n=28), or 12 weeks of nitazoxanide followed by 36 weeks of nitazoxanide plus standard of care treatment (a triple regimen, n=28). An additional 24 interferon-experienced patients were randomized to receive 12 weeks of nitazoxanide followed by either the dual regimen (n=12) or the triple regimen (n=12) for 36 weeks. Patients received 180 microgram injections of pegylated interferon (Pegasys®) once per week; nitazoxanide was administered as one 500 mg tablet twice daily; and ribavirin was administered as 1,000 or 1,200 mg daily according to weight.

Results
At 12 weeks following the end of treatment, naïve patients who received a triple regimen that included standard of care and nitazoxanide showed a significantly higher SVR (HCV RNA < 10 IU/mL, Abbott m2000) than the group receiving the standard of care regimen (79% vs. 43%, respectively) (p=0.006). The data also suggest a potential for eliminating or reducing the role of ribavirin in treating hepatitis C. Patients treated with a dual regimen of nitazoxanide and peginterferon showed an SVR at week 12 following the end of treatment that was not inferior to standard of care (68% vs. 43%, respectively) (+25%; 95% CI: -1%, +47%). Of 24 treatment-experienced patients, the triple regimen (n=12) resulted in an SVR of 25% at week 12 post- treatment, and the dual regimen group (n=12) had an SVR of 8%.

"Results from this trial validate a new approach to treating HCV that focuses on the interaction between the virus and the cell," said Jean-François Rossignol, M.D., Director of the Romark Institute for Medical Research. "With confirmation provided by this data we are aggressively pursuing development of nitazoxanide and related drugs to treat chronic hepatitis C and other viral diseases."

Nitazoxanide is the first of a new class of small molecule drugs called thiazolides that inhibit replication of a broad range of viruses. The drug was discovered by Dr. Rossignol and was initially developed by Romark and approved for marketing in the United States as the first treatment of cryptosporidiosis. Serendipitously, the development of nitazoxanide for treating cryptosporidiosis led to the discovery of its antiviral properties and ultimately to the discovery of a promising new class of antiviral drugs.

Romark is currently conducting a U.S. Phase II trial with nitazoxanide plus standard of care in patients with hepatitis C genotype 1 who were previously treated with interferon. The Company also plans to initiate a Phase II trial in treatment naïve patients early in 2008.

[3txsofar]

As I look closer at this Ain Shams U. study published in Hepatology 2007, the goofier it looks.  If I take a weighted average of the three variable length treatment arms, I get 68% SVR, which is more than the control arm of 58%.  But all arms got the same drugs, the only difference being shorter treatment for RVR and EVR.  Weird!

[jmjm530]

3tx: but one needs to consider that pegylated interferon alone can give a more than 80% SVR for type 4
-------------------------------
That appears only to hold true for RVRs (group A).  This study suggests overall SVR rates between 32.4% and 54.9%, depending on sub type, with the 54.9% sub-type the one most prevelant in Egypt where I believe they trialed Alinia. Yes, slightly better results than with genotype 1, but a far cry from the 80% figure, if that was meant to be an overall figure -- but maybe I just read it wrong.

http://www.hivandhepatitis.com/hep_c/news/2007/071007_b.html

[3txsofar]

The following was posted on yahoo finance -vertx by pinvestment

"it is amazing what people will latch on to

it will be interesting to see what VRTX has to say tonight as the street.com says it is holding an investor meeting tonight and will report additional data tomorrow morning
but one needs to consider that pegylated interferon alone can give a more than 80% SVR for type 4

so the new data that is considered to be so damaging for VRTX is actually for a genotype of HepC that is already very easy to treat with interferon alone

check it out for yourself

Pegylated interferon alpha-2b plus ribavirin in patients with genotype 4 chronic hepatitis C: The role of rapid and early virologic response.

Kamal SM, El Kamary SS, Shardell MD, Hashem M, Ahmed IN, Muhammadi M, Sayed K, Moustafa A, Hakem SA, Ibrahiem A, Moniem M, Mansour H, Abdelaziz M.
Department of Gastroenterology and Hepatology, Ain Shams University, Cairo, Egypt.
In patients chronically infected with hepatitis C virus (HCV) genotype 4, the optimum duration of therapy and the predictors of sustained virologic response (SVR) have not been adequately determined. In this study, 358 patients with chronic hepatitis C genotype 4 were randomly assigned to pegylated interferon (PEG-IFN) alpha-2b (1.5 mug/kg/week) plus oral ribavirin (10.6 mg/kg/day) for a fixed duration of 48 weeks (control group, n = 50) or for a variable duration (n = 318). In the variable-duration group, patients with undetectable HCV RNA at week 4 were treated for 24 weeks (group A, n = 69), patients with undetectable HCV RNA at week 12 were treated for 36 weeks (group B, n = 79), and the rest of the patients were treated for 48 weeks (group C, n = 160). The primary endpoint was SVR (undetectable HCV RNA 24 weeks after treatment cessation). Groups A-C and the control group had SVR rates of 86%, 76%, 56%, and 58%, respectively. After the study was controlled for predictors, a low baseline histologic grade and stage were associated with SVR (P < 0.029) in all groups. In addition, among patients in group C, older age (P = 0.04), a higher baseline body mass index (P = 0.013), and low baseline HCV RNA (P < 0.001) were also associated with SVR attainment. The incidence of adverse events and the rate of discontinuation were higher in patients in the variable-duration and fixed-duration groups treated for 48 weeks. Conclusion: In patients with chronic hepatitis C genotype 4 and undetectable HCV RNA at weeks 4 and 12, treatment with PEG-IFN alpha-2b and ribavirin for 24 weeks and 36 weeks, respectively, is sufficient. (HEPATOLOGY 2007.). "

[drofi]

and off-label money is money too. Some nice reports here and there work well.
We compare apples and pears by looking to different genotypes, patient populations, and conformity levels to GCP.

SVR-rate from SOC is 70% in Genotype 1, just creat a nice design:

Gastroenterol Clin Biol. 2007 Aug-Sep;31(8-9 Pt 3):20-8:
Larrey D, Couzigou P, Denis J.
The treatment of chronic hepatitis C, now well codified with the association of a pegylated interferon alpha and ribavirin, allows to obtain a prolonged virological response in more than half of the cases. The results are even better and reach about 70% of success when the treatment is optimized.

Nevertheless, I am excited to read the report about answers to critical questions from the Boston meeting.

Best regards, Drofi

[gauf]

You are right to be skeptical. These results raise questions that need to be addressed, I am of the opinion that if it can't hurt to add it to SOC, then I want to add it. I am waiting with bated breath to see what HR has to report on it from the conference. Hope he posts as soon as he can.

[3txsofar]

I have some further Alinia observations, based on the above article and the original post in this thread.  The above article showed standard of care achieving SVR of 55% in Egyptian genotype 4 patients.  The control group in the the Alinia study only achieved 43%, which is a huge difference and would make me wonder about the integrity of the study.

The Alinia study reported 79% SVR at 12 weeks, which could decline as it reaches 24 weeks.  More importantly though you have to wonder how does 79% for Genotype 4 translate to SVR for genotype 1?  Certainly the success for geno 1 would be less, but how much?  On top of that, there is the questionable integrity of the study.

Personally, I have a lot of questions about the Alinia study.  Why did they go to Egypt, where standards for the trial are more lax?  Why Genotype 4, when every other major drug seems to start with 1?  Were they simply trying to get some headlines so they could get some off-label  use?

I would have much more confidence in a company that started trials in Europe or the USA with genotype 1 patients.  

This whole thing reminds me of leatrile clinics in Tijuana for cancer patients.